Term
|
Definition
| Glycoprotein that contains N-linked, O-linked, and GAG polysaccharides / can bind to and cross link many ECM components / Important in basal lamina / abnormalities can cause dwarfism |
|
|
Term
|
Definition
| Glycoproteins that contain GAG polysaccharides |
|
|
Term
|
Definition
| Multi-adhesion protein commonly found in basement membranes / Can bind collagen, sulfated lipids, axons, and dendrites |
|
|
Term
|
Definition
| Most abundant multi-adhesion protein in the ECM |
|
|
Term
|
Definition
| Unbranched polysaccharides usually (uronic acid and an amino sugar) / They contain negative charge from carboxylic acid and sulfate functional group... thus imbibe lots of water / Found in cartilage / Usually bound to a protein core |
|
|
Term
| Core proteins of proteoglycans |
|
Definition
| involved in mediating signals from the outside of the cell to the interior / GAG may extend extracellularly while the core proteins produce cytosolic signals when GAG binds to ligand ig Syndecan-4 |
|
|
Term
|
Definition
| Often a result of cartilage degeneration (more specifically the proteoglycan Aggrecan and type II collagen) |
|
|
Term
|
Definition
| Location: Cartilage Function: Mechanical support, forms large aggregrates with hyaluronic acid (support), binds to TGF-Beta (stops ECM production) |
|
|
Term
|
Definition
| Location: Widespread in ECM Function: Bings to type I collagen fibrils (limits size) |
|
|
Term
|
Definition
| Two nearly identical polypeptide joined by two disulfide bonds/ Has various globular domains for ECMs or specific domains to bind / Cell surface receptors receptors binds domains have RGD which is recognized by fibronectin receptor |
|
|
Term
| Where and when is Laminin produced? |
|
Definition
| Epithelial and endothelial cells and is important for neuronal development / One of the first |
|
|
Term
| Loss of function laminin-1 |
|
Definition
| Causes cell division to be arrested very early in development |
|
|
Term
| Major Protein Components of the Basal Lamina |
|
Definition
| Collagen: Type IV / Proteoglycan: Perlecan / Multi-adhesive matrix protein: Laminin / ENTACTIN: protein cross-linker |
|
|
Term
|
Definition
| Bind by homophilic (same to same) interactions / Present in desmosomes and mediate cell adhesion in development |
|
|
Term
|
Definition
| Bind by homophilic (same to same) interactions / Similar to Ig structure / Important in neuronal development |
|
|
Term
|
Definition
| Heterophilic interactions / Bind to multi-adhesion matrix proteins (fibronectin) |
|
|
Term
|
Definition
| Heterophilic interactions / Carb binding proteins, binding glycoproteins of other cells |
|
|
Term
| What cellular function are selectins important for? |
|
Definition
| Extravasation of leukocytes, movement of WBC from capillaries to tissues |
|
|
Term
| Injured tissues, platelets, and endothelial cells all express what during an injury? |
|
Definition
| PAF: Platelet activating factor |
|
|
Term
| What does PAF do in a cell? |
|
Definition
| It causes endothelial cells to express P-selectins? |
|
|
Term
| What happens when WBC selectin binds to p-selectin on the endothelial cell? |
|
Definition
| PAF binds to the PAF receptor |
|
|
Term
| What happens after PAF binds to the PAF receptor? |
|
Definition
| Adhesion of the WBC and endothelial cell occurs via WBC integtin and an Intercellular Adhesion Molecule (ICAM)... then extravastion |
|
|
Term
| What does a reduction of leukocyte extravasation also reduce? In what disease would this be useful for and why? |
|
Definition
| Inflammation / Multiple Sclerosis / Stops chronic inflammation |
|
|
Term
|
Definition
| Drug that reduces inflammation by blocking extravasion by WBC |
|
|
Term
| What motifs do many integrins recognize? |
|
Definition
| Acidic AA's like RGD motifs (infibronectin) |
|
|
Term
|
Definition
| Cell surface integrins can have active and inactive states depend on the state of the cell |
|
|
Term
|
Definition
| proteins that mediate interactions with the cytoplasmic cytoskeleton |
|
|
Term
| Paxillin-Focal Adhesion Kinase (FAK) |
|
Definition
| Uses Ras-MAP Kinase pathway to initiate cell signalling via integrins / used in polymerization of Actin Stress Fibers |
|
|
Term
| What intracellular signaling pathway proteins can integrins activate? And what will it do? |
|
Definition
| ERK1/2, P13K pathway, Rac/Rho/Cdc42 G-proteins / cytoskeleton, cell proliferation, cell survival, cell migration, and gene transcription |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Hetero-oligosaccharides or hetero-polysaccharides that contain more than one species of monosaccharides. Complex carbohydrates are usually linked to proteins and lipids to form glycoproteins and glycolipids. |
|
|
Term
|
Definition
| Glycoproteins and glycolipids / The 3 major classes of glycoconjugates found in higher animals are glycoproteins, proteoglycans and glycosphingolipids. |
|
|
Term
| Structural Representation of Glucose |
|
Definition
| What makes D vs L, alpha vs beta, what is more prevalent, yaddy yaddy |
|
|
Term
| What is the driving force for the cyclization of the open chain Fisher D-Glucose form to closed Hayworth D-Glucose form |
|
Definition
|
|
Term
| Biochemical Basis of Protein Glycation |
|
Definition
The first step of protein glycation
is the formation of a Schiff base.
The aldehyde group of glucose
reacts with an amino group of a
protein to form a Schiff base, or
an aldimine. This step is reversible. Since glucose contains an OH group at carbon 2, next to the Schiff base, the
Schiff base can undergo an Amadori rearrangement to form a stable ketoamine. These two steps are the most important steps for protein glycation. |
|
|
Term
|
Definition
HbA1C is formed by glycation of the N-terminal valine of the two β-chains in HbA (Figure 4). The two Nterminal valine residues of the two β-chains can react with two residues of the open chain form of glucose to form two Schiff bases or pre-HbA1C. The two Schiff bases undergo Amadori
rearrangement to form two stable ketoamines or HbA1C. |
|
|
Term
| Change from Glucose: Mannose |
|
Definition
| Mannose is the C-2 epimer of glucose . |
|
|
Term
| Change from Glucose: Galactose |
|
Definition
| Galactose is a C-4 epimer of D-glucose. |
|
|
Term
Change from Glucose: D-Nacetylglucosamine
(GlcNAc) |
|
Definition
Derived from D-glucose by modifying
the C-2 hydroxyl group into an Nacetyl
group. |
|
|
Term
| Change from Glucose: D-glucuronic acid |
|
Definition
| Converting the CH2OH at carbon 6 of D-glucose with a COOH group |
|
|
Term
| Change from D-Glucuronic acid: L-Iduronic acid |
|
Definition
| Epimerization of carbon 5 of D-glucuronic acid converts this sugar to L-iduronic acid |
|
|
Term
Change from D-Nacetylglucosamine
(GlcNAc): N-Acetylgalactosamine |
|
Definition
| C-4-epimer of D-N-acetylglucosamine |
|
|
Term
| What is required for a glycosidic linkage? |
|
Definition
nucleotide sugar donor, a sugar
acceptor, and a glycosyltransferase |
|
|
Term
| What are the major nucleotide sugar donors in glycosidic linkages? |
|
Definition
UDP-sugar donors, GDP sugar donors and CMP-sugar donors. UDP
sugar donors include UDP-Gal, UDP-Glc,
UDP-GlcA, UDP-GalNAc and UDPGlcNAc.
GDP-sugar donors include
GDP-Man and GDP-Fuc. CMP sugar
donors are CMP-N-acetylneuraminic acid and CMP-N-glycolylneuraminic acid (sialic acid donors). |
|
|
Term
| Where in the cell does the biosynthesis of sugar chains take place? |
|
Definition
| The ER and the Golgi complex |
|
|
Term
| Biosynthesis of lactose in mammary gland? |
|
Definition
Requires a sugar acceptor modifier for beta-galactosyltransferase. This
modifier is α-lactalbumin, which is
produced in the mammary gland. In the
presence of α-lactalbumin, the acceptor for β-galactosyltransferase is glucose and the product is lactose |
|
|
Term
| Biosynthesis of lactose in mammary gland: in the absence of alpha-lactalbumin. |
|
Definition
| the normal acceptor for β-galactosyltransferase is N-acetylglucosamine and the product is N-acetyllactosamine. |
|
|
Term
|
Definition
Cleaves sugar chains / lactose is
cleaved by beta-galactosidase or lactase to produce galactose and
glucose |
|
|
Term
|
Definition
|
|
Term
| What is the most common O-glycosidic linkage? |
|
Definition
| The alpha-glycosidic linkage between N-acetylgalactosamine and SER and THR on a peptide chian |
|
|
Term
| An N-linked sugar chain is linked to a polypeptide chain... how? |
|
Definition
through the
β-N-glycosidic linkage between Nacetylglucosamine
and Asn on a polypeptide chain |
|
|
Term
| N-Glycans can be divided into “high mannose type” and “complex type.” Describe the difference... |
|
Definition
High mannose type N-glycans contain
only N-acetylglucosamine and mannose. Complex type N-glycans contain Gal and sialic acid in addition to Nacetylglucosamine and mannose. |
|
|
Term
| High mannose type (or neutral type) sugar chain |
|
Definition
contains two Nacetylglucosamine
attached to an Asn followed by a
beta-linked mannose (in red) and several alpha-linked
mannose residues at peripheral positions of the sugar chain. |
|
|
Term
A complex type (or acidic type)
sugar chain |
|
Definition
contains N-acetylglucosamine, galactose,
and sialic acid at the peripheral position of the sugar
chain. |
|
|
Term
| What do mannose type and complex sugar chains have in common? |
|
Definition
| There structural root and the Asn is always next to the consensus sequence, X-Serine or Threonine |
|
|
Term
| Major Steps in the Biosynthesis of N-Glycans |
|
Definition
| Step 1 for the biosynthesis of N-glycans involves the assembly of a high mannose type sugar chain on the lipid carrier Dolichol phosphate. The next step is the transfer of the high mannose type sugar chain from Dolichol phosphate to an Asn residue of a nascent peptide chain. Step 3 involves the processing of the high mannose type sugar chain into a complex type sugar chain. |
|
|
Term
|
Definition
The high mannose type sugar chain "carrier" / Transfers chain to Asn of a nascent peptide chain / The lipid carrier dolichol phosphate is embedded
in the ER. The first step involves the stepwise assembly of a neutral type or high mannose type sugar chain on this lipid carrier. The addition of 3 glucose residues to the sugar chain signifies the completion of the assembly. |
|
|
Term
| Congenital Disorders of Glycosylation (CDG) |
|
Definition
Congenital Disorders of Glycosylation are a group of disorders of abnormal synthesis of N-glycans caused by
deficiency in over 20 different enzymes associated with the synthesis of N-glycans. |
|
|
Term
|
Definition
| Condroitin sulfate / Each aggrecan monomer contain a core protein to which around chondroitin sulfate and 30-50 keratan sulfate GAG chains are attached / Each GAG is covalently linked to the core protein through a Serine-Xylose-Galactose-Galactose sequence. |
|
|
Term
| Aggrecans and hyaluronic acid |
|
Definition
|
|
Term
|
Definition
| Glucuronic acid (GlcA) and N-Acetylgucosamine (GlcNAc) joined by Beta 1-3- linkage and a Beta 1-4 for the next disaccaride / Vitreous humor of the eye, synovial fluid of joints and loose connective tissue / The only GAG that does not link to a core protein |
|
|
Term
|
Definition
| GlcA and N-Acetylgalactosamine and Carbon 4 is sulfated / Acidic - amino link: beta 1-3 / in cartilage, tendons, and ligaments |
|
|
Term
|
Definition
| GlcA and N-Acetylgalactosamine and Carbon 6 is sulfated / Acidic - amino link: beta 1-3 / in cartilage, tendons, and ligaments |
|
|
Term
|
Definition
| L-Iduronic acid and N-Acetylgalactosamine and Carbon 6 is sulfated / Acidic - amino link: ALPHA 1-3 / in cartilage, tendons, and ligaments |
|
|
Term
|
Definition
| Composed of Galactose and GlcNAc joined by BETA-1,4- link / Then GluNAc is linked to the next Gal through a BETA 1,3 link / Disaccharide is called N-Acetyllactosamine / Carbon 6 often sulfated / Found in cartilage and cornea |
|
|
Term
| Heparin and Heparan Sulfate |
|
Definition
| Composed of either L-iduronic acid (L-IdoA) or D-GluA AND D-glucosamine (D-GlcN)via 2 ALPHA-1,4 link or 1 ALPHA and 1 BETA (if D-GluA) / HP and HS are the only GAGs that have an alpha linked GluN / Some carbons are usually sulfated or can be acetylated |
|
|
Term
|
Definition
| Disorders caused by the abnormal catabolism of three specific GAGs (lysosomal storage diseases). (DS, HS, and KS) <== You need to recognize the differences in sugars |
|
|
Term
| Gram Positive vs Gram Negative |
|
Definition
| Positive = thick peptidoglycan layer / Negative = thin peptidoglycan layer |
|
|
Term
| Chemical nature of peptidoglycan |
|
Definition
| Contain GlcNAc and N-acetylmuramic acid (MurNAc) (BETA 1,4), which is GlcNAc conjugated with lactic acid in an ether linkage |
|
|
Term
| Polysaccharide Chain of Peptidoglycan |
|
Definition
| Contain GlcNAc and N-acetylmuramic acid (MurNAc) (BETA 1,4), which is GlcNAc conjugated with lactic acid in an ether linkage / A tetrapeptide side chain (D-glutamate, L-lysine w/ 5 glycine residues, and D-alanine) is attached to the lactic acid MurNAc / |
|
|
Term
| Formation of the Bacterial Peptidoglycan Cell Wall |
|
Definition
| Pentaglycine or one strand and the D-alanine on the neighboring strand (cross link) / Catalyzed by transpeptidase / BETA lactum inhibits transpeptidase cross linking |
|
|
Term
|
Definition
| All are autosomal recessive except MPS II |
|
|
Term
|
Definition
| MPS1 = Hurler (Last on DS and HS), MPS II = Hunter (Last on DS and HS), MPS III = Sanfilippo (2nd on HS), MPS IV = Morquio (Last on KS) |
|
|
Term
| Enzyme responsible for deficiency in MPS II (Hunter) |
|
Definition
| Iduronate sulfastase (removes sulfate) |
|
|
Term
| Enzyme responsible for deficiency in MPS I (Hurler) |
|
Definition
| ALPHA-L-Iduronidases (cleaves iduronic acid) |
|
|
Term
| Enzyme responsible for deficiency in MPS III (Sanfilippo) |
|
Definition
| Heparan N-sulfatase, Acetyl-CoA acetyl transferase, and ALPHA-N-acetyl-glucosaminidase |
|
|
Term
| Enzyme responsible for deficiency in MPS IV (Morquio) |
|
Definition
| Galactose 6-sulfatase or BETA Galactosidase |
|
|
Term
What is the main structural difference
between this GAG and other GAGs? |
|
Definition
Among various GAGs only heparin and
heparan sulfate contain alpha-linked
glucosamine. It should be noted that
heparin and heparan sulfate are
structurally related. |
|
|
Term
| What, my dear man, is a GSL? |
|
Definition
| information-rich glycoconjugates that occur in nature, mainly as constituents of biological membranes. Each GSL contains a hydrophilic sugar chain linked to a hydrophobic ceramide. The ceramide anchors the molecule into the membrane. |
|
|
Term
|
Definition
Comprised of a fatty acid, which is acylated to a sphingosine backbone / can act as signaling molecules to
regulate differentiation,
proliferation, and apoptosis / Water permeability barrier |
|
|
Term
| The two GSLs that contain only one sugar residue... |
|
Definition
galactosylceramide and glucosylceramide (both shown in
red). Between these two, galactosylceramide is the major GSL
of the CNS, while glucosylceramide is mainly found in visceral organs. |
|
|
Term
|
Definition
| Formed by adding a galactose to glucosylceramide through a β-1, 4 linkage ( |
|
|
Term
|
Definition
| Formed by adding a galactose to the terminal galactose of lactosylceramide through an α-1, 4 linkage |
|
|
Term
|
Definition
| Formed by adding an GalNAc to the terminal galactose of Gb3 through a β-1, 3 linkage |
|
|
Term
| Catabolism of Gb4 and the disease association |
|
Definition
The catabolism of Gb4 yields Gb3, and the terminal β-linked GalNAc is removed (hydrolyzed, Figure 5). The enzymes that catalyze this reaction are β-hexosaminidase A and B.
This step is blocked in a total β-hexosaminidase deficiency, or type O Tay-Sachs disease, leading to the accumulation of Gb4 in the lysosome. |
|
|
Term
| BETA-Hexosaminidase: (Hex) A and Hex B |
|
Definition
Hex A and Hex B
can cleave both BETA-linked GluNAc and BETA-linked GalNAc
structures. Hex A is a heterodimer consisting of 1 α and 1 BETA
subunit. Hex B consists of 2 BETA subunits. |
|
|
Term
| Catabolism of Gb3 and disease association |
|
Definition
In the catabolism of Gb3, the α-linked terminal galactose in Gb3 is hydrolyzed by alpha-galactosidase
A to release galactose and lactosylceramide. A mutation in the gene that encodes α-galactosidase A
causes the impaired degradation of Gb3. The inability to catalyze this step, and the accumulation of Gb3 in
the lysosome causes Fabry disease. |
|
|
Term
|
Definition
| Active enzyme in Gb3 catabolism / Can remove galactose from Gb3 and then if still active lactosylceramide |
|
|
Term
| Catabolism of GlcCer (Glucosylceramide) and associated disease |
|
Definition
Glucosylceramide (or glucocerebroside) is hydrolyzed by
glucocerebrosidase (or β-glucosidase) to produce glucose and
ceramide. The inability to catalyze this reaction, and
the accumulation of Glucosylceramide in the lysosome causes
Gaucher disease. |
|
|
Term
| Catabolism of GalCer (Galactosylceramide) and associated disease |
|
Definition
Galactosylceramide (or Galactocerebroside) is hydrolyzed
by Galactocerebrosidase (GALC or β-galactosidase) to
produce galactose and ceramide. The inability to catalyze this reaction, and the accumulation of Galactosylceramide in the lysosome causes Krabbe disease. |
|
|
Term
|
Definition
| All contain sialic acid N-Acetylnueraminic Acid (NeuAc): GM3, GM2, and GM1 |
|
|
Term
|
Definition
| Shortest chain / N-acetylneuraminic acid is attached to the terminal Galactose of the neutral GSL, lactosylceramide / GM3 is the major ganglioside found in visceral organs. |
|
|
Term
|
Definition
Formed by attaching an
GalNAc to the galactose of GM3 through a β- 1,4 linkage. The inability to degrade GM2 in the lysosome causes Tay-Sachs disease. |
|
|
Term
|
Definition
| GM1 is formed by attaching Galactose to the terminal GalNAc of GM2 through a β-1,3 linkage. GM1 is the major ganglioside of the CNS and GM1 is a receptor for cholera toxin. |
|
|
Term
| “G” Nomenclature of Gangliosides |
|
Definition
| The nomenclature for gangliosides was created by Lars Svennerholm (Figure 12). G means ganglioside and M means the number of sialic acids. In GM1, there is only one sialic acid (NeuAc), so the ganglioside is monosialosyl. The number 1 is derived from 5-n, where n is the number of sugar residues in the main sugar chain. In GM1 there are 4 sugar residues in the main chain. Therefore, - 4 = 1. |
|
|
Term
| Catabolism of GM1 and associative disease |
|
Definition
| In the catabolism of GM1, the terminal galactose (in red) is hydrolyzed by β-galactosidase, releasing Galactose and GM2 (Figure 13). The inability to catalyze this reaction (due to a deficiency of β-galactosidase), and the accumulation of GM1 in the lysosome causes gangliosidosis (or generalized gangliosidosis). |
|
|
Term
| Catabolism of GM2 and associative disease |
|
Definition
In the catabolism of GM2, the enzyme β-Hexosaminidase A and in the presence of a protein co-factor referred to as GM2-activator, the terminal GalNAc is hydrolyzed. This releases GalNAc and GM3. The inability to catalyze this reaction, and the accumulation of GM2 in the
lysosome causes Tay-Sachs disease. We will elaborate the enzymatic deficiencies that can cause variants of Tay-Sachs disease in the discussion session. |
|
|
Term
| Catabolism of GM3 and associative disease |
|
Definition
In the catabolism of GM3, the enzyme Sialidase (or Neuraminidase)
catalyzes the hydrolysis of NeuAc, generating NeuAc and Lactosylceramide. Lactosylceramide is then subsequently converted to Glucosylceramide by β-galactosidase. |
|
|
Term
|
Definition
Historically the "O-group": This sugar
chain contains an L-fucose and galactose together by an α-1, 2 linkage. |
|
|
Term
|
Definition
| If GalNAc is attached to the H-antigen, then the H-antigen is converted to the A-antigen and this trisaccharide is the blood group A determinant. It has GalNAc as the terminal sugar. |
|
|
Term
|
Definition
If Galactose is attached to the H-antigen, then the Hantigen
is converted to the B-antigen, and this galactose-containing trisaccharide defines the blood group B determinant. |
|
|
Term
What is the reason for blood group
incompatibility transfusion? |
|
Definition
| Presence of reciprocal antibodies in the serum of people whose RBCs lack the corresponding antigen(s). For example, type A individuals have anti-B antibody in their serum. |
|
|
